The biosynthesis of melanin is collectively regulated by over 100 distinct genes. In mammals, three enzymes, tyrosinase (TYR), tryosinase-related protein-1 (TRP-1) and tryosinase-related protein-2 (TRP-2) are essential for the overall melanin production. Tyrosinase performs a pivotal role in the modulation of melanogenesis. It is the rate-limiting enzyme that catalyzes the hydroxylation of L-tyrosine into 3,4-dehydroxyphenylalanine (DOPA) and consequently oxidizes DOPA into DOPA quinone. TRP-2, which serves as a DOPA-chrome tautomerase (DCT), further promptly coverts DOPA quinone into 5,6-dihydroxyindol-2-carboxylic acid (DHICA), whereas TRP-1 facilitates the oxidization of DHICA to form carboxylated indole-quinone. Two types of melanin are produced: a red/yellow pheomelanin and a black/brown eumelanin. The TYR enzyme is critically involved in both pheomelanin and eumelanin synthesis while TRP-1 and DCT contribute more in the synthesis of eumelanin. Microphthalmia-associated transcription factor (MITF) is a primary transcriptional activator of the melanogenic enzymes and seems to be the principle transcription regulator that mediates the survival, proliferation and differentiation of melanoblasts and melanocytes. Given that melanin synthesis in mammal involves multiple-step catalyzation that modulated by a group of enzymes and transcription factors, it is important to understand the biological molecular mechanisms of melanogenesis inhibitors.
In mammals, skin pigments are produced in the melanosomes of melanocytes cells that are situated on the basal layer between the dermis and epidermis. The pigmentation plays a crucial role in terms of protecting skin against radiation-induced damage such as exposure to ultraviolet light. However, overproduction or abnormal accumulation of melanin may lead to many skin hyperpigmentation disorders including freckles, age spots, post-inflammatory hyperpigmentation and even melanoma. Undesired excessive skin pigmentation is a severe health concern since it can cause negative burdens on patients' psychological well-being. Thus, skin depigmentation remains a compelling research area for the cosmetic industry and the exploration of novel classes of safe and effective melanogenesis inhibitors from natural sources has attracted immense research interest.
There remains a need, therefore, for improved skin whitening compounds with enhanced skin whitening capabilities.